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In Case You Missed It:

Protecting the heart from cancer therapy

Published: March, 2010

Battling cancer can have long-term effects on the heart.

Treating cancer isn't yet a precise science. Although doctors are
getting better at targeting tumors, there's still no magic bullet
that homes in on cancer cells and destroys them without risking
collateral damage to other parts of the body. The outward signs
of off-target destruction include classic side effects of
chemotherapy and radiotherapy such as hair loss, nausea, and
fatigue. But there can be silent inner damage, too, sometimes to
the heart and arteries. These injuries can appear immediately
during therapy; other times they don't surface for years.

"Important advances in our ability to fight cancer over the last
few decades have translated into improved survival," says Dr.
Erica L. Mayer, an oncologist at Harvard-affiliated Dana-Farber
Cancer Institute. "But we are also learning that many of these
lifesaving therapies have the potential to affect the heart and
other parts of the body."

Once relegated to the back burner, the late effects of cancer
care are gradually getting more attention. One turning point was
the publication in 2005 of From Cancer Patient to Cancer
Survivor: Lost in Transition. This influential report from
the Institute of Medicine put a spotlight on the disjointed care
often received by the 12 million-plus cancer survivors in the
United States after their cancer treatment has ended.

The report has led to greater awareness by cancer specialists of
the long-term physical, medical, and psychological needs of
cancer survivors. One important item that's still in development:
evidence-based strategies for the best way to monitor cancer
survivors for late effects of cancer therapy.

A delicate balance

Most cancer-fighting techniques exploit cancer cells' tendency to
grow quickly and divide rapidly. By interrupting the mechanics of
cell division, chemotherapy and radiation therapy can stop cancer
in its tracks. But since these therapies can't yet tell bad cells
from good ones, they also affect healthy cells that grow and
divide rapidly, like hair follicles and cells lining the stomach
and intestines. Heart cells grow and divide very slowly. This
makes them less sensitive to the effects of cancer therapy, but
not impervious to it.

Fighting cancer is tricky business. The goal is to hit the cancer
with effective doses of chemotherapy or radiation while
minimizing side effects elsewhere in the body. Because these
therapies can save lives, patients and doctors have traditionally
tolerated long-term side effects. But as specialists develop more
precise ways to deal with cancer, there is increasing emphasis on
minimizing short- and long-term complications.

Chemotherapy

The drugs used to fight cancer extend life for millions of people
and sometimes eradicate the disease completely. In doing so, they
can also inadvertently harm the heart and arteries. Some
chemotherapies can trigger immediate problems, such as blood
vessel spasms or irregular heart rhythms, while others can set
off slow changes that accelerate artery-clogging atherosclerosis
or lead to heart failure.

Drugs often linked to heart damage include the anthracyclines and
anthraquinolones — doxorubicin, daunorubicin, epirubicin,
mitoxantrone, and others. They are used to treat a variety of
cancers, including leukemia, lymphoma, and cancers of the breast,
uterus, ovary, and lung. At high cumulative doses, these drugs
can weaken the left ventricle, the heart's main pumping chamber,
leading to heart failure. To prevent this from happening, doctors
try to make sure that the lifetime dose of these medicines stays
below the threshold for heart problems.

Trastuzumab (Herceptin) is an antibody treatment for one type of
breast cancer. Treatment with trastuzumab has led to improvements
in survival for women with this type of cancer. But it, too, can
weaken the left ventricle. That's why women receiving trastuzumab
should have their heart function monitored closely during
treatment. Platinum-based agents like cisplatin, a mainstay for
treating testicular cancer, can damage the inner lining of
arteries, causing spasms that can lead to chest pain (angina) or
Raynaud's disease.

The cardiac side effects of anthracyclines, trastuzumab,
cisplatin, and other chemotherapy agents may be seen early, as
treatment is under way. Temporarily stopping the drug, lowering
the dose, or starting treatment with an ACE inhibitor or other
heart-protecting medicine are ways to allow chemotherapy to
continue. However, cardiac side effects can also emerge decades
after treatment is completed. That's why it is important to be
vigilant for new symptoms that could herald changes in heart
function. Research to make chemotherapy less dangerous for the
heart is under way.

Cardiac cancer — uncommon but possible

Heart cells grow and multiply at a glacial pace. Although
this presents problems for healing after a heart attack,
it makes the heart a relatively rare site for cancer. Yet
cardiac cancer does occur. In the United States each
year, several hundred people are diagnosed with tumors
that originate in the heart (primary cardiac cancer).
Many others develop cardiac tumors that have spread from
elsewhere in the body (secondary or metastatic cancer).
Up to three-quarters of all primary heart tumors are
benign, meaning they don't grow in an unlimited,
aggressive manner, don't invade surrounding tissues, and
don't spread to other tissues (metastasize). Yet even
benign tumors can interfere with the heart's vital
function.

Primary cardiac tumors. Myxomas
(mick-SOE-mahs) are the most common type of cardiac
tumor. If detected and treated early, these benign tumors
have little effect on lifespan. Most malignant primary
cardiac cancers are soft-tissue tumors known as sarcomas.
They tend to grow rapidly inside the heart and quickly
spread to other tissues. This type of cancer is rare.

Metastatic cardiac tumors. Cancer cells
that break away from tumors elsewhere in the body can
grow in the heart. Almost any type of cancer can do this,
but the most likely ones include lung, breast, skin
(melanoma), stomach, and ovarian cancer. These secondary
or metastatic tumors are far more common than primary
cardiac tumors.

Effects on the heart

Any cardiac tumor can jeopardize the heart's ability to
pump blood by preventing the heart from contracting,
blocking blood flow into or out of the heart, taking up
space inside one of its chambers, or interfering with the
operation of a valve.

General, nonspecific symptoms of heart trouble are
usually the first indications of a cardiac tumor.
Unexplained shortness of breath, fainting, palpitations,
chest pain, and fever are some of the most common
symptoms. Swelling in the face or legs or distended veins
in the neck are physical signs that sometimes herald a
cardiac tumor. Still, the rarity of cardiac cancer
coupled with symptoms that usually indicate more common
forms of heart disease, such as heart failure or an
infection of the heart, make pinning down the diagnosis
difficult.

Treatment

Benign cardiac tumors are usually removed surgically.
Survival following removal of a myxoma is often
excellent. In a 48-year survey of surgery for cardiac
tumors at the Mayo Clinic, people who had a myxoma
removed lived as long as average Americans of the same
age and gender.

The outlook for malignant primary or metastatic tumors is
less favorable. Surgery and chemotherapy can extend
survival, but don't always completely eradicate the
cancer. Improving symptoms is often the focus of
treatment.

Radiation therapy

Although heart tissue is relatively resistant to the effects of
radiation, it is sometimes damaged by radiotherapy around the
chest wall for breast, lung, or esophageal cancer or lymphoma. A
side effect that appears early is pericarditis, inflammation of
the protective sac around the heart (the pericardium). Radiation
can also set off slower chains of events that lead to a range of
cardiovascular problems, including valve trouble and rhythm
problems. It can also cause premature stiffening and narrowing of
the heart's arteries, which increases the chances of having a
heart attack. Radiation-related damage to arteries can sometimes
complicate later bypass surgery or angioplasty.

Post-radiation cardiovascular disease was much more common with
older techniques used before the late 1980s. Newer radiation
techniques, including 3-D planning with CT scans and tightly
focused radiation beams, let doctors more precisely target tumors
and shield the heart and other healthy tissues. Improvements in
these technologies and the development of new ones will almost
certainly further reduce the risk of radiation-related heart
damage.

Hormone therapy

Some cancers are strongly influenced by hormones. Estrogen
nurtures breast cancer; testosterone fuels prostate cancer. Drugs
that block the production of these hormones, or cells' responses
to them, can stifle cancer. They can also have some
cardiovascular consequences.

Tamoxifen, an anti-estrogen used for treating breast cancer,
somewhat increases the risk of potentially harmful blood clots
(deep-vein thrombosis and pulmonary embolism). Men who take
testosterone-blocking drugs for prostate cancer are slightly more
likely to have heart attacks or develop diabetes or other
cardiovascular problems compared with men who don't take these
drugs.

Vigilant survivorship

As experts study the effects of cancer therapy on the heart and
rest of the body, there are many things a cancer patient can do
to be a healthy survivor.

"If you are undergoing treatment for cancer, the best thing you
can do is pay attention to your body," advises Dr. Edward T.H.
Yeh, who chairs the cardiology department at M.D. Anderson Cancer
Center in Houston. If you are short of breath or develop chest
pain or swelling in your legs, tell your oncologist so he or she
can immediately refer you to a cardiologist. "It's all about
collaboration, driven by the patient," says Dr. Yeh.

The same advice applies once you've finished treatment. Keeping
on top of standard risk factors — like smoking, blood pressure,
cholesterol, weight, physical activity, diet, and stress — can
help prevent the appearance of heart disease. Being vigilant for
signs of heart disease, and reporting them to your doctor, is
equally important.

If life were completely fair, cancer survivors would be exempt
from future health problems. Sadly, that isn't the case. Cancer
survivors are prone to heart disease like everyone else, and
perhaps a bit more so as a result of cancer therapy. Overall,
cancer therapy saves lives, and doesn't cause long-term problems
for most survivors. But since it is impossible to tell who will
develop later complications, knowing that they can occur is
important information to have.